Multifunctional Thermosensitive Liposomes Based on Natural Phase Change Material: Near-Infrared Light-Triggered Drug Release and Multimodal Imaging Guided Cancer Combination Therapy.

Multifunctional theranostic nanoplatforms (NPs) in response to environment stimulations for on-demand drug release are highly desirable. Herein, the near-infrared (NIR)-absorbing dye, indocyanine green (ICG) and the antitumor drug, doxorubicin (DOX) were efficiently co-encapsulated into the thermosensitive liposomes based on natural phase change material (PCM). Folate and conjugated gadolinium chelate-modified liposome shells enhance active targeting and magnetic resonance (MR) performance of the NPs while maintaining the size of the NPs. The ICG/DOX loaded and gadolinium chelates conjugated temperature-sensitive liposomes nanoplatforms (ID@TSL-Gd NPs) exhibited NIR-triggered drug release and prominent chemo-, photothermal, photodynamic therapy properties. With the co-encapsulated ICG, DOX and the conjugated gadolinium chelates, the ID@TSL-Gd NPs can be used for triple-modal imaging (fluorescence/photoacoustic/magnetic resonance imaging, FL/PAI/MRI) guided combination tumor therapy (chemotherapy, photothermotherapy and photodynamic therapy, Chemo/PTT/PDT). After tail vein injection, the ID@TSL-Gd NPs accumulated effectively in subcutaneous HeLa tumor of mice. The tumor was effectively suppressed by accurate imaging guided NIR triggered phototherapy and chemotherapy, and no tumor regression and side effects were observed. In summary, the prepared ID@TSL-Gd NPs achieved multimodal imaging-guided cancer combination therapy, providing a promising platform for improving diagnosis and treatment of cancer.